MN Gene and Protein

Abstract

Identified herein is the location of the MN protein binding site, and MN proteins/polypeptides that compete for attachment to vertebrate cells with immobilized MN protein. Such MN proteins/polypeptides prevent cell-cell adhesion and the formation of intercellular contacts. The MN protein binding site is a therapeutic target that can be blocked by organic or inorganic molecules, preferably organic molecules, more preferably proteins/polypeptides that specifically bind to that site. Therapeutic methods for inhibiting the growth of preneoplastic/neoplastic vertebrate cells that abnormally express MN protein are disclosed. Vectors are provided that encode the variable domains of MN-specific antibodies and a flexible linker polypeptide separating those domains. Further vectors are disclosed that encode a cytotoxic protein/polypeptide operatively linked to the MN gene promoter, and which vectors preferably further encode a cytokine. The MN gene promoter is characterized, and the binding site for a repressor of MN transcription is disclosed.

1 - 30 . (canceled) 
     
     
         31 : An organic or inorganic molecule that specifically binds the enzymatic center of the carbonic anhydrase domain of MN protein, said domain comprising amino acid sequence SEQ ID NO: 51, and said molecule being useful in treating preneoplastic and/or neoplastic disease, which is characterized by abnormal expression of MN protein. 
     
     
         32 : The organic or inorganic molecule of  claim 31  wherein said molecule, when in contact with a vertebrate preneoplastic or neoplastic cell that abnormally expresses MN protein, inhibits the growth of said cell. 
     
     
         33 : The molecule of  claim 31  which is organic. 
     
     
         34 : The molecule of  claim 33  which is a protein or a polypeptide. 
     
     
         35 : The molecule of  claim 34  wherein said protein or polypeptide comprises a peptide selected by screening a phage display peptide library for specific binding to said domain. 
     
     
         36 : The polypeptide of  claim 35 , wherein said polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 107, 108 and 109. 
     
     
         37 : The polypeptide of  claim 36 , wherein said: polypeptide has an amino acid sequence selected from the group consisting of SEQ ID NO: 107, 108 and 109. 
     
     
         38 . A method of identifying an organic or an inorganic molecule that binds specifically to a site within the enzymatic center of the carbonic anhydrase domain of a MN protein, said domain comprising amino acid sequence SEQ ID NO: 51, said method comprising identifying molecules that bind the said MN protein and are eluted by a carbonic anhydrase inhibitor as specifically binding to the said site, and the said molecule being useful in treating preneoplastic and/or neoplastic disease, which is characterized by abnormal expression of MN protein. 
     
     
         39 : The method of  claim 38  wherein said carbonic anhydrase inhibitor is a sulfonamide. 
     
     
         40 : The method of  claim 38  wherein said carbonic anhydrase inhibitor is acetazolamide. 
     
     
         41 : The method of  claim 38  wherein the said molecule is inorganic. 
     
     
         42 : The method of  claim 38  wherein the said molecule is organic. 
     
     
         43 : The method of  claim 42  wherein the said molecule is a protein or a polypeptide. 
     
     
         44 : The method of  claim 43  wherein the said protein or polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOS: 107, 108 and 109. 
     
     
         45 : The method of  claim 43  wherein the said polypeptide is selected from the group consisting of SEQ ID NOS: 107, 108 and 109. 
     
     
         46 : The method of  claim 38  wherein the said organic or inorganic molecule, when in contact with a vertebrate preneoplastic and/or neoplastic cell that abnormally expresses MN protein, inhibits the growth of said cell.